Albumin, especially human serum albumin (HSA), is an important protein of the circulatory system. The protein is produced in the liver and has a major role in maintaining normal osmotic pressure of body fluids, such as blood. It also serves as a carrier of various molecules.
HSA is administered under various clinical conditions. For example, in the case of shock or burn injury, it is necessary, in general, to administer HSA frequently to restore blood volume and to alleviate other injury-related symptoms. Patients suffering from hypoproteinemia and fetal erythroblastosis sometimes require HSA treatment.
In other words, a common indication for HSA administration is a loss of body fluids, such as during a surgical procedure, shock, burn injury or hypoproteinemia which causes edema.
Currently, HSA is produced mainly as a fractionated product of collected blood. Such a production process, however, has disadvantages in that it is not economical and the supply of blood is sporadic. In addition, collected blood sometimes contains undesirable substances, such as hepatitis virus. In consequence, it is profitable to develop a material which can be used as an HSA substitute.
Recent advances in recombinant DNA techniques have rendered possible microbial production of various types of useful polypeptides, and, as a result, a number of mammalian polypeptides already have been produced in various microorganisms. With regard to HSA, establishing techniques for the large scale production of HSA by recombinant methods and subsequent high grade purification also is in progress.
Techniques for the isolation and purification of HSA from plasma have been studied from various points of view and put into practical use. For example, the ethanol fractionation method of E. J. Cohn et al., PEG fractionation method, ammonium sulfate fractionation method and the like are well known methods. In addition to those methods, several purification processes recently have been developed, such as, for example, a process in which an anion exchanger treatment and a heat treatment at 60.degree. C. for 10 hours are employed in combination (JP-A-2-191226 corresponding to EP-A-367220) and a process in which an anion exchanger treatment, a cation exchanger treatment and a heat treatment at 60.degree. C. for 10 hours are employed in combination (JP-A-3-17123 corresponding to EP-A-428758). (The term "JP-A" as used herein means an "unexamined published Japanese patent application".)
However, in the case of producing HSA by means of gene manipulation techniques, it is highly probable that an HSA preparation of interest will be contaminated by certain coloring components which are contained in the raw materials or secreted by a microorganism during culturing of the host microorganism or are introduced during purification of the resulting HSA, and that those contaminants bind to HSA to cause coloring of the HSA itself. What is more, such contaminants cannot be removed sufficiently by means of any prior art process for the purification of plasma-derived HSA.